Modification of the resting-state network involved at different stages of neuropathic pain.

Neuropathic pain (NeuP) is shown to be associated with abnormal changes in several specific brain regions. However, the large-scale interactivity of neuronal networks underlying the sensory and emotional abnormalities during NeuP remains unexplored. The present study aimed to explore the alterations in the relevant functional resting-state networks (RSNs) and their intra-networks at the different stages of NeuP based on resting-state functional magnetic resonance imaging (rs-fMRI). A NeuP rat model was established by chronic constriction injury (CCI). Three RSNs were identified to be associated with the NeuP, including the default mode network (DMN), sensorimotor network (SMN), and interoceptive network (IN). The functional connectivity (FC) of the left caudate putamen (CPu) within the DMN and the right piriform cortex within the IN were significantly reduced at the early stage of NeuP, when the maximum allodynia was apparent early, which reflected the suppressed function of the DMN and IN. At 4 weeks post-CCI, when negative emotions were present, the FC of the right insular cortex in the SMN and left visual cortex in the IN were significantly elevated, representing the increased excitability of both SMN and IN. Our study revealed the characteristic functional organization at the network level induced by NeuP and emphasized the role of SMN, DMN, and IN in the pathological mechanisms of NeuP.

Brain Functional Alteration at Different Stages of Neuropathic Pain With Allodynia and Emotional Disorders.

Neuropathic pain (NeuP), a challenging medical condition, has been suggested by neuroimaging studies to be associated with abnormalities of neural activities in some brain regions. However, aberrancies in brain functional alterations underlying the sensory-discriminative abnormalities and negative emotions in the setting of NeuP remain unexplored. Here, we aimed to investigate the functional alterations in neural activity relevant to pain as well as pain-related depressive-like and anxiety-like behaviors in NeuP by combining amplitude of low frequency fluctuation (ALFF) and degree centrality (DC) analyses methods based on resting-state functional magnetic resonance imaging (rs-fMRI). A rat model of NeuP was established via chronic constriction injury (CCI) of the sciatic nerve. Results revealed that the robust mechanical allodynia occurred early and persisted throughout the entire observational period. Depressive and anxiety-like behaviors did not appear until 4 weeks after injury. When the maximum allodynia was apparent early, CCI rats exhibited decreased ALFF and DC values in the left somatosensory and nucleus accumbens shell (ACbSh), respectively, as compared with sham rats. Both values were significantly positively correlated with mechanical withdrawal thresholds (MWT). At 4 weeks post-CCI, negative emotional states were apparent and CCI rats were noted to exhibit increased ALFF values in the left somatosensory and medial prefrontal cortex (mPFC) as well as increased DC values in the right motor cortex, as compared with sham rats. At 4 weeks post-CCI, ALFF values in the left somatosensory cortex and DC values in the right motor cortex were noted to negatively correlate with MWT and exhibition of anxiety-like behavior on an open-field test (OFT); values were found to positively correlate with the exhibition of depressive-like behavior on forced swimming test (FST). The mPFC ALFF values were found to negatively correlate with the exhibition of anxiety-like behavior on OFT and positively correlate with the exhibition of depressive-like behavior on FST. Our findings detail characteristic alterations of neural activity patterns induced by chronic NeuP and underscore the important role of the left somatosensory cortex, as well as its related networks, in the mediation of subsequent emotional dysregulation due to NeuP.

[Therapeutic effect of Fanzhen Jieci needling on discogenic sciatica: a randomized controlled trial].

OBJECTIVE: To compare the therapeutic effect between Fanzhen Jieci (warming acupuncture plus fast needling) combined with conventional acupuncture and simple conventional acupuncture on discogenic sciatica. METHODS: A total of 76 patients with discogenic sciatica were randomized into a Fanzhen Jieci group and a conventional acupuncture group, 38 cases in each one. Conventional acupuncture was applied at Shenshu (BL 23), Dachangshu (BL 25), L1-L5 Jiaji (EX-B 2) and Huantiao (GB 30) on the affected side, etc. in the conventional acupuncture group. On the basis of the treatment in the conventional acupuncture group, Fanzhen Jieci was applied at L1-L5 Jiaji (EX-B 2) and Huantiao (GB 30) on the affected side in the Fanzhen Jieci group, i.e. warming acupuncture was applied at L1-L5 Jiaji (EX-B 2), and fast needling was applied at Huantiao (GB 30) on the affected side for a depth of 40-60 mm, so as to introduce a sensation of electric shock transmitting to lower limb, and then the needle was immediately withdrawn. The treatment was given once every other day, 3 times a week for 3 weeks in both groups. The visual analogue scale (VAS) score of leg and low back pain, the Oswestry disability index (ODI) score and the 36-item short form health survey (SF-36) score before and after treatment were compared between the two groups. RESULTS: Compared before treatment, the VAS scores of leg and low back pain and the ODI scores after treatment were decreased in both groups (P<0.001), the changes of the VAS scores of leg and low back pain in the Fanzhen Jieci group were larger than those in the conventional acupuncture group (P<0.05). After treatment, except for the role emotional and health transition scores, the various scores of SF-36 were increased compared before treatment in the Fanzhen Jieci group (P<0.01); except for the role physical, role emotional and health transition scores, the various scores of SF-36 were increased compared before treatment in the conventional acupuncture group (P<0.01). After treatment, the physical functioning, role physical, bodily pain, mental health and general health scores of SF-36 in the Fanzhen Jieci group were higher than those in the conventional acupuncture group (P<0.05). CONCLUSION: Fanzhen Jieci combined with conventional acupuncture can effectively relieve the pain and improve the mental state in patients with discogenic sciatica, its therapeutic effect is superior to simple conventional acupuncture.

A network pharmacology approach to predict potential targets and mechanisms of "Ramulus Cinnamomi (cassiae) - Paeonia lactiflora" herb pair in the treatment of chronic pain with comorbid anxiety and depression.

BACKGROUND: Traditional Chinese medicine (TCM) prescriptions have multiple bioactive properties. "Gui Zhi-Shao Yao" herb pair is widely used to treat chronic pain (CP), as well as anxiety and depression. However, its related targets and underlying mechanisms have not been deciphered. METHODS: In this study, the network pharmacology method was used to explore the bioactive components and targets of "Gui Zhi-Shao Yao" herb pair and further elucidate its potential biological mechanisms of action in the treatment of CP with comorbid anxiety disorder (AD) and mental depression (MD). RESULTS: Following a series of analyses, we identified 15 active compounds, hitting 130 potential targets. After the intersections the targets of this herb pair and CP, AD and MD - sorted by the value of degree - nine targets were identified as the vital ones: Akt1, IL6, TNF, PTGS2, JUN, CASP3, MAPK8, PPARγ and NOS3. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results demonstrated 11 pathways, such as AGE-RAGE signalling pathway, IL-17 signalling pathway, TNF signalling pathway, which primarily participate in the pathological processes. CONCLUSIONS: This study preliminarily predicted and verified the pharmacological and molecular mechanisms of "Gui Zhi-Shao Yao" herb pair for treating CP with comorbid AD and MD from a holistic perspective. In vivo and in vitro experiments will be required to further investigate the mechanisms.KEY MESSAGEA network pharmacology approach was applied to identify key targets and molecular mechanisms.Nine targets were regarded as the vital targets for chronic pain with comorbid anxiety and depression.Predicted 11 pathways were the potential therapy targets and pharmacological mechanism of "Gui Zhi-Shao Yao" herb pair.

"Fan-zhen Jie-ci" acupuncture therapy for treatment of discogenic sciatica: protocol for a single-blind, randomized controlled clinical trial.

BACKGROUND: Curative medical treatment for patients with discogenic sciatica is limited. Acupuncture is an important non-pharmacological therapy reported to have positive therapeutic effects on discogenic sciatica. According to traditional Chinese acupuncture theory, discogenic sciatica is a channel tendon disease which can be treated by a special "Fan-zhen Jie-ci (FZJC)" method. Our recent preliminary clinical evidence indicated that the FZJC method had a positive treatment effect on the disease. This study will further evaluate the efficacy and safety of FZJC on patients with discogenic sciatica. METHODS: A single-blind randomized controlled clinical trial will be conducted, assigning 76 participants with discogenic sciatica to a randomly assigned FZJC group or a control group. Acupuncture treatment combined with the FZJC method will be applied in the FZJC group while routine acupuncture treatment only will be applied in the control group. Treatments will be administered three times a week for a total of 3 consecutive weeks. The primary outcome of this trial is change in the visual analogue scale of leg pain (VAS-LP), and the secondary outcomes are changes in the visual analogue scale of back pain (VAS-BP), the Brief Pain Inventory (BPI), the Oswestry Disability Index (ODI), the 36-Item Short Form Health Survey (SF-36), and serum concentrations of mitochondrial DNA (mtDNA) and high sensitivity C reactive protein (hsCRP). DISCUSSION: The results of this study will provide insight into the efficacy and safety of FZJC acupuncture as a treatment for discogenic sciatica. TRIAL REGISTRAION: The trial has been registered at the Chinese Clinical Trial Registry (ChiCTR1900026272) and the Acupuncture-Moxibustion Clinical Trial Registry (AMCTR-IOR-19000275).